This article describes
how a natural alkaloid allocryptopine (ALL)
is able to differentiate two forms of biologically relevant human
telomeric (htel22) G-quadruplex DNAs (GQ-DNA) depending on the presence
of K+ and Na+ ions by steady-state and time-resolved
spectroscopic techniques. For both interactions, predominant involvements
of static-type quenching mechanism with the negligible influence of
dynamic collision are established by UV–vis absorption and
fluorescence emission study, which is further supported by fluorescence
lifetime measurements. ALL exhibits appreciable affinity toward both
GQ-DNAs. Both the mixed-hybrid (3 + 1) quadruplex structures in K+ ions and the basket-type antiparallel quadruplex structure
under Na+ condition are converted to parallel types in
the presence of ALL. Fluorescence intercalator displacement assay
experiment revealed modest selectivity of ALL to both quadruplexes
over duplex DNA along with higher selectivity for antiparallel types
among the two quadruplexes via groove and/or loop binding, which is
distinct from the conventional π-stacking of the ligands on
external G-quartets. ALL stabilized both GQ-DNA topologies moderately.
The differences in the dynamics of ALL within both DNA environments
have been demonstrated vividly by time-resolved anisotropy measurements
using the wobbling-in-cone model. These results suggest groove binding
with antiparallel G-quartet with high affinity and moderate loop binding
with mixed-hybrid G-quartet accompanied by the partial end stacking
additionally in both of the cases. Our conclusions are further supported
by steady-state anisotropy measurements and molecular docking. The
present investigation can be used in the development of a biocompatible
antitumour/anticancer agent targeting particular GQ-DNA conformation.
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